RT Journal Article
SR Electronic
T1 RADX Sustains POT1 Function at Telomeres to Counteract RAD51 Binding, which Triggers Telomere Fragility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.20.912634
DO 10.1101/2020.01.20.912634
A1 Anna-Sophia Briod
A1 Galina Glousker
A1 Joachim Lingner
YR 2020
UL http://biorxiv.org/content/early/2020/02/27/2020.01.20.912634.abstract
AB The 3’ terminal DNA extensions at chromosome ends can become engaged into multiple biochemical reactions during DNA replication, telomerase-mediated telomere extension, homology directed DNA repair, nucleolytic processing and DNA damage checkpoint activation. To keep these activities in check, telomeric 3’ overhangs can be hidden in t-loop structures or they associate with specialized proteins such as POT1. Here, we explore the telomeric microenvironment using a proximity-dependent labeling approach and identify the oligonucleotide/oligosaccharide-binding (OB)-fold containing protein RADX. RADX binds single-stranded telomeric DNA throughout the cell cycle along with POT1, suppressing accumulation of fragile telomeres, which are indicative of telomere replication defects. Telomere fragility in POT1 and RADX double-depleted cells was due to accumulation of the RAD51 recombinase at telomeres. RADX also supports DNA damage signaling at POT1-depleted telomeres counteracting RAD51 binding. Thus, RADX represents next to POT1 a second OB-fold containing single-strand telomere binding protein sustaining telomere protection.